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Séminaire impromptu - Natàlia CarullaDefining the oligomer form/s responsible for amyloid-beta neurotoxicity in Alzheimer ́s disease

Abstract :


 Amyloid-beta (A beta) oligomers are considered the pathogenic form of A beta in Alzheimer ́s disease (AD).
However, their heterogeneous and transient nature have precluded definition of the term neurotoxic A beta oligomer, thus preventing the development of therapeutic strategies that target them. Inspired by functional and structural changes associated to AD, such as oxidative stress and membrane disruption, we have developed strategies, namely chemical cross-linking and the use of detergent micelles, to prepare A beta oligomers with well-defined properties. Using these samples, we are obtaining crucial information on the chemical and structural features that define beta oligomer neurotoxicity, critical to treat AD.

Short bio

Natàlia Carulla was born in Barcelona, Spain. She obtained her B.Sc. in Chemistry from the University of Barcelona in 1996 and her Ph.D. in Biological Chemistry from the University of Minnesota in 2001. The same year, she moved to the University of Cambridge to work as a Marie Curie post-doctoral researcher in Prof. Christopher M. Dobson laboratory in the field of protein misfolding. Protein misfolding and subsequent aggregation into amyloid fibrils is central to increasingly prevalent disorders such as Alzheimer’s and Parkinson’s diseases. During her time in Cambridge, Natàlia developed and applied new approaches for the dynamic characterization of amyloid fibrils using a model system. In 2004, she returned to Barcelona to the laboratory of Prof. Ernest Giralt at the Institute for Research in Biomedicine (IRB Barcelona), where she extended the project initiated in Cambridge and developed an approach to structurally characterize the intermediates formed during amyloid fibril formation, which had been imputed as the pathogenic agents in amyloid diseases. In 2011, she was awarded a Ramon y Cajal fellowship from the Spanish Government, which enabled her to start her own research program at IRB Barcelona. Her research aims at establishing the links between aggregation of the amyloid-beta peptide (A beta) and Alzheimer ́s disease (AD). Specifically, it seeks to contribute to a detailed molecular level understanding of A beta aggregation both in solution and in a membrane environment with the goal of establishing the basis for the development of rational—and therefore potentially successful—therapeutic strategies through which AD can be prevented or cured.